TP53 is a classic tumor suppressor, but its role in kidney cancer remains unclear. In our study, we tried to explain the role of p53 in kidney cancer through the p53-related enhancer RNA pathway. Functional experiments were used to explore whether P53-bound enhancer regions 2 (p53BER2) has a role in the cell cycle and senescence response of TP53-wild type (WT) renal cancer cells in vitro or vivo. RNA-sequencing was used to identify the potential target of p53BER2. The results showed that the expression level of P53BER2 was downregulated in renal cancer tissues and cell lines, further dual-luciferase experiments and APR-256-reactivated experiments showed p53BER2 expresses in a p53-dependent way. Moreover, knockdown p53BER2 could reverse nutlin-3-induced cytotoxic effect in TP53-WT cell lines. Further exploration showed the downregulation of p53BER2 could reverse nutlin-3-induced G1-arrest and senescence in TP53-WT cell lines. What is more, the knockdown of p53BER2 showed resistance to nutlin-3 treatment in vivo. Additionally, we found BRCA2 could be regulated by p53BER2 in vitro and vivo; further experiment showed p53BER2 could induce cell-cycle arrest and DNA repair by mediating BRCA2. In summary, the p53-associated enhancer RNA-p53BER2 mediates the cell cycle and senescence of p53 in TP53-WT renal cancer cells.

Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals.

Previous reports about laparoscopic total pelvic exenteration (LTPE) are still limited. In the present study, we described our single-center experience of the initial 11 cases. Between April 2011 and September 2015, eight males and three females diagnosed as pelvic malignancies underwent LTPE by the same operation team. We retrospectively collected all cases’ parameters about surgical technique. Thirty-seven patients who received open surgery were also retrospectively collected. A comparison between LTPE and open surgery was performed to evaluate the feasibility and safety of LTPE. Eleven cases successfully underwent the LTPE without any intraoperative complication. No open conversion was required. Eight patients underwent Bricker’s procedure. Three patients were performed with the cutaneous ureterostomy. Anus preservation operation was performed in three patients. Compared with open surgery, LTPE had longer mean operative time (565.2 vs 468.2 min, p = 0.004) but less mean blood loss (547.3 vs 1033.0 ml, p < 0.001) and shorter postoperative hospitalization time (15.3 vs 22.4 days, p = 0.004). One patient died of pulmonary embolism in the 7th month of follow-up time. One patient died of recurrence in the 12th month of follow-up time. Nine patients are still alive without recurrence and metastasis. The mean follow-up time was 11.1 months. The technique of LTPE seems to be feasible and safe in the treatment of carefully selected patients of pelvic malignancies. LTPE can also decrease the blood loss, the recovery time, and the hospital stay. But the oncological safety and long-term outcome of LTPE still need to be explored.

Von Hippel‐Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age‐related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age‐related risks for the five major VHL‐associated tumors were evaluated using Kaplan–Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age‐adjusted telomere length ≤ 0.44) suffered higher age‐related risks for VHL‐associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age‐related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL‐associated tumors.